RU2703395C1 - Method of combined surgical stimulation of lower extremity chronic lower limb neoangiogenesis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to vascular surgery, and can be used for treating patients with chronic, critical ischemia of lower extremities of mainly III and IV degrees, in occlusion diseases of arteries with involvement of distal arterial bed, when the use of direct reconstructive operations on the vessels is impossible, and the pharmacological, physical and biological techniques for stimulating the collateral blood circulation remain ineffective. Method involves trephine opening. Through osteoperforatory holes are made on all extremities, using clamp of "mosquito" type and stupidly passing through all layers of tissue to bone. In the formed holes, a guiding protective tube is inserted into which a drill is installed. On thigh through 10 separate punctures of skin and wide fascia of hip with length of up to 1.0 cm along outer surface accesses to external surface of femur, wherein in projection of proximal epiphysis of femur, from level 5 cm below greater trochanter, through every 4–5 cm in distal direction along external surface exactly in middle of bone through inserted before bone protective tube guide by drill with diameter of 4.5 mm in transverse direction in center performing three through perforations, passing both cortical layers before the sponge substance content is applied from the drill guide and is filled with a red scarlet substance. In the projection of the diaphysis in the transverse direction at the center of the external surface at a distance of up to 4–5 cm from each other, 4 damages are performed by drilling in the external layer of the periosteum without a dip into the intramedullary canal; 3 perforated holes of distal metaepiphysis are made at distance of 4–5 cm from each other in proximal direction, projecting first bone drilling from level of upper edge of patella. On the shin the through perforations of the proximal and distal phalangees of the tibia, 3 per each, are performed monotonously, as on the femur, but the direction of drilling is performed from the inner surface of the shin. 4 damages by drilling in outer layer of periosteum, without a dip into medullary canal, in diaphyseal part on medial surface of shin bone are performed also at distance of up to 4–5 cm from each other, through muscular massif of anterior region of shin. On the foot of one prick on the inner surface of the heel, 1.5 mm Kirshner wire, the heel bone is perforated "in-line", through, without removing the pin from the prick three times in different directions, and on the side of I metatarsal bone, at a distance of up to 3 cm between the injections, transverse through tunneling of I-II-III-IV metatarsal bones is performed twice; through the produced orifices with syringe of 20.0 ml, introducing the autologous autoconcentrate of stem cells with a total volume of 100 ml into the soft tissues and the osteoperforation zones on the thigh, on ankle additionally and in muscular mass of anterior, external and posterior osteo-fibrous sheaths, on foot in I-II-III-IV, intercellular spaces.

EFFECT: method provides expansion of reserve vessels, precapillaries and lumen of surviving vessels, creates prerequisites for stimulation of neoangiogenesis, improving possibility of collateral microcirculatory blood flow due to differentiation of introduced stem cells (SC), leads to activation of tissue perfusion and increased capacity of peripheral vascular bed in ischemic tissues along entire length of involved limb.

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Description

The invention relates to medicine, namely to vascular surgery, and can be used to treat patients with chronic, critical ischemia of the lower extremities, mainly of the III and IV degrees, with occlusive arterial diseases with damage to the distal arterial bed, when the use of direct reconstructive operations on the vessels is impossible, and pharmacological, physical and biological methods of stimulating collateral circulation remain ineffective. The method is intended to expand the reserve vessels, precapillaries and lumen of the preserved vessels, creates the prerequisites for the stimulation of neoangiogenesis that improves the ability of collateral microcirculatory blood flow. Due to the differentiation of introduced stem cells (SC), it leads to activation of tissue perfusion and an increase in the capacity of the peripheral vascular bed in ischemic tissues along the entire length of the affected limb.

The most difficult problem for surgeons is the treatment of chronic lower limb ischemia caused by multiple "multi-story" stenosis and vascular occlusion with a lack of an adequate microvasculature. In these cases, direct arterial reconstruction is often not possible, and the progression of the disease leads to the development of critical ischemia and gangrene [Savelyev B.C., Koshkin V.M., Karalkin A.V. Pathogenesis and conservative treatment of severe stages of atherosclerosis obliterans of lower limb arteries. - M .: MIA, 2010.216 s .; Bosiers M., Schneider P.A. Critical limb ischemia. N.-Y .: Informa Healthcare USA. 2009. 352 p.]. The mortality rate of patients with CINC during the first year of the development of the syndrome is from 25% to 70% [Pokrovsky A.V. Ischemic diabetic foot / A.V. Pokrovsky, V.N. Dan, A.V. Chupin // medical scientific Internet magazine "MedWeb". - 2002. - No. 2. S. 18-35, Boqueria, L.A. Cardiovascular Surgery / L.A. Boqueria, R.G. Gudkova - M.: Publishing House of the NCCSSH im. A.N. Bakuleva, 2013 .-- S. 129-134; Deneuville, M. Survival and quality of life after arterial revascularization or major amputation for critical leg ischemia in Guadeloupe / M. Deneuville // Ann. Vase Surg. 2006. Vol. 20, No. 6. P. 753-760], and 5-year survival is only 40% [Sorokin V.A. Treatment of critical lower limb ischemia with bone revascularization: Abstract. dis, cand. honey. sciences. - Vladivostok, 1999 .-- 22 p .; Stepanov N.G. The quality of life of the patient and its duration after amputation / N.G. Stepanov // Angiology and Vascular Surgery. 2004. - No. 4. - S. 13-16; TASC Working Group Inter-Society Consensus for the Management of Peripheral Arteria disease // Eur. J. Vase. Endovasc. Surg. 2007. Vol. 33. - Suppl. 1. - P. 1-431.]. For these reasons, amputation of the limb is often the only way to extend the life of the patient. Dissatisfaction with the treatment results necessitates the search for new effective methods of revascularization of the affected limb, aimed at increasing the compensatory capabilities of the microvasculature (increasing volumetric blood flow in the limb segments), due to the stimulation of the capacity of microcirculatory circulation and neoangiogenesis.

Along with lumbar sympathectomy (PSE), which has been in the arsenal of angiosurgeons for over 80 years [G. Prokhorov Alentiev A.A., Sukhov V.K. The effect of lumbar sympathectomy on tissue blood flow in the limb with obliterating atherosclerosis // Herald of Surgery. I.I. Grekov. - 1989. - T. 144. - No. 8, - S. 45-50; Kokhan E.P. Lumbar sympathectomy in the complex treatment of obliterating diseases of the lower extremities Text. / E.L. Kokhan, O.V. Pinchuk // Angiology and Vascular Surgery. - 1997. - T. 3. - No. 1, - S. 128-134 .; Burleeva E.P., Smirnov O.A. Reflections on chronic critical ischemia. Angiol and vessel chir 1999; 1: 17 23], other methods of indirect limb revascularization are also used, such as corticotomy according to G.A. Ilizarov [Ilizarov G.A., Zusmanovich F.N. A method for the treatment of chronic lower limb ischemia. A.S. 1061803, 1983, USSR], revascularizing osteotrepanation (ROT) [Shabanov AN, Kotelnikov VP Pathogenesis and treatment of obliterating endarteritis. M., 1983 .-- 121 s .; Fokin A.A., Verbovetsky L.P., Fokin Al. An., Kulak A.N. The effectiveness of the method G.A. Ilizarova in the treatment of patients with stages III and IV of chronic lower limb ischemia // Herald of surgery. - 1990. - T. 145. - No. 11. - S. 15-20; Zusmanovich F.N. A new method for activating collateral circulation is revascularizing osteotrepanation // West. chir. - 1991. - No. 5, 6. - S. 114-115; Zusmanovich F.N. Revascularizing osteotrepanation (ROT) in the treatment of patients with obliterating diseases of the extremities. - Kurgan, 1996.292 s .; Burov Yu.A., Moskalenko A.N., Gavrilov V.A., Migulskaya E.G. Combined lower limb revascularization in patients with critical ischemia // Angiology and Vascular Surgery. 2000. - No. 4. - S. 86-89., 2000; Konstantinov B.A., Milanov N.O., Gavrilenko A.V. et al. Surgical treatment of chronic critical ischemia of the lower extremities in case of insolvency of the distal vascular bed // Thoracic and cardiac

vascular surgery. 2001. - No. 3. - S. 58-63.], Extravasation of autologous blood according to the method of P.F. Life (Genesis P.F., Chikale E.T. Stimulation of blood flow in the limbs with obliterating lesions of arteries // Surgery. 1982, No. 7. - P. 102-105.), Epidural and bone electrical stimulation (Horsh S., Klayes L. Epidural electrical stimulation of the spinal cord in obliterating diseases of the peripheral arteries // Herald of Surgery. - 1995. - T. 154. - No. 4-6. - P. 111-113.), Autologous transplantation of a large omentum (Zatevakhin II. Transplantation of a large gland using microsurgical technique for thromboangiitis obliterans. Surgery. 1984, 5, pp. 61-66; RF patent N 21244313 , А61В 17/00, Method for the surgical treatment of peripheral blood circulation disorders with occlusive diseases of the lower limb arteries (Poyarkov V.D., Baykov A.N.); RF patent N 2136222, А61В 17/00, 17/56, Method for the surgical treatment of obliterating diseases of the vessels of the lower extremities (Nevash EE, Pulin AG, Nefedov IP), laser exposure to muscles and bones of the ischemic limb, etc. However, most of the proposed methods are excessively traumatic, require equipment for microvascular intervention and special skills, can provoke the development of gross trophic disorders, require a long stay of the patient in the hospital, and do not always prove to be effective [Kuznetsov MR, Evgrafov AI, Turkin PA Surgical treatment of chronic lower limb arterial insufficiency: current state of the problem (literature review) // Thoracic and cardiovascular surgery. 2002. - No. 2. - S. 56-59; Agarwal V.K. Long-term results of omental transplantation in chronic occlusive arterial disease (Buergers disease) // Int. Surg. 2005. Vol. 90, No 3. P. 167-174 .; Ma Z., Bian J., Yuan S. Application of one-stage arteriovenous shunt to circulation reconstruction for extensive arterial ischemic disease of lower extremities // Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2006. Vol. 20, No 12.1. P. 1168-1171].

The operation of revascularizing osteotrepanation (ROT) is designed to activate bone marrow blood flow, the disclosure and improvement of the function of the paraossal, muscle and skin collaterals. A sharp increase in the number of vessels is explained by the reflex opening of the so-called reserve vessels, which are normally in a collapsed state and do not function [Krupko I.L. The laws of reparative regeneration of bone tissue and the ability to control the course of fracture fusion / I.L. Krupko // Materials of the 2nd Congress of Orthopedic Traumatologists of the USSR. M., 1969. - S. 74-76; Lavrishchev, G.I. Reparative regeneration of bones in various conditions: Abstract. dis. Dr. med. sciences / G.I. Lavrishchev. M., 1969. - 16 p.]. At a later date, from 2-4 weeks to 3-6 months, after a bone injury, reflex arterial hyperemia of the entire limb develops, the lumen of the main vessels and precapillaries widens, the number of small-caliber vessels increases [Strokov V.N., Nikitenko I.K. . The clinical significance of changes in regional blood circulation in the treatment of fractures and false joints by compression-distraction osteosynthesis // Treatment of fractures and their consequences by transosseous osteosynthesis: Vseros. scientific prakt. lonf. - Kurgan, 1979.- S. 234-237 .; Onoprienko G.A., Suvalyan A.G. Vascularization of the tibia in conditions of closed osteosynthesis with a massive pin // Orthopedist, traumatol. 1986. - No. 9. - S. 40-42 .; Shevtsov V.I. Bunov B.C., Schurova E.N. The combined effect of bone tunneling and drug therapy on blood circulation in patients with obliterating atherosclerosis of the lower extremities // Geniuses of Orthopedics. - 1997. - No. 2. - S. 54-57.]. During reparative regeneration of bone, its vascularization is characterized by the predominant development of new arterial vessels [Sazonova B.A., Amosov I.S., Morozova T.I. Vascularization of bone regenerate // VI Congress of Radiologists and Radiologists of the Ukrainian SSR: / Thes. doc. /. - Kiev, 1978. - S. 173-175; Fokin A.A., Kulak A.N. The effectiveness of the method G.A. Ilizarova in the treatment of patients with stages III and IV of chronic lower limb ischemia // Herald of surgery. - 1990. - T. 145. - No. 11. - S. 15-20]. According to the theory of Krompeher P.S. (1979) in response to trauma, especially to a bone fracture, the stem undifferentiated cells are ejected from the bone marrow, forming a network of the smallest, with no characteristic identification of vessels, between the ends of the fragments. These vessels contain a large amount of blood necessary for the full implementation of the process of reparative regeneration [Larionov A.A. Comparative evaluation of revascularization of a massive free autograft during distraction and compression of a long tubular bone // Archive of Anatomy, Histology and Embryology. - 1990. - No. 11. - S. 5-11 .; Larionov A.A., Rechkin M.Yu., Schurova E.N., Filimonova G.N. Stimulation of blood circulation in the tissues of the limb by repeated perforations. Bulletin of Traumatology and Orthopedics. N.N. Pirogov - 2004. - No. 1. - from. 53-56].

The best results were obtained by the authors of the ROT technique in patients with stage II B and stage III disease. The mechanism of the positive influence of this operation is not fully understood and is discussed in the literature [Burov Yu.A., Moskalenko AN, Gavrilov VA, Migulskaya EG Combined lower limb revascularization in patients with critical ischemia // Angiology and Vascular Surgery. 2000. - No. 4. - S. 86-89]. The operation is effective for distal and diffuse forms of atherosclerosis and inflammatory diseases, if it is impossible to perform vascular reconstruction [Fokin A.A., Verbovetsky L.P., Fokin Al. An., Kulak A.II. The effectiveness of the method G.A. Ilizarova in the treatment of patients with stages III and IV of chronic lower limb ischemia // Bulletin of surgeons and. - 1990. - T. 145. - No. 11. - S. 15-20 .; Kamyshov S.A. Revascularizing osteotrepanation in the complex surgical treatment of critical lower limb ischemia: Abstract. dis, cand. honey. sciences. - Irkutsk, 2004. - 5 p .; Egorov A.A. Clinical and pathogenetic aspects of the operation of revascularizing osteotrepanation in patients with arteriosclerosis obliterans of the lower limb arteries: Abstract. dis., cand. honey. sciences. - Ryazan, 2007. - 22 p.]. The ROT technique is constantly being improved, and now there is its laser counterpart, called laser osteotrepanation, which has a positive effect in 65.5% of cases [Giniatullin F.R. Experimental and morphological substantiation of the method of surgical treatment of chronic limb ischemia using high-intensity laser radiation: Abstract. dis, cand. honey. sciences. - Chelyabinsk, 2003. - 7 p.].

In 1982, G.A. Ilizarov and F.N. Zusmanovich proposed a method for treating chronic limb ischemia - a.s. 1061803 USSR, MKI A61B 17/00 (G.A. Ilizarov, F.N. Zusmanovich), based on the principle of distraction of bone fragments using a special apparatus. Under the influence of “tensile stress”, neoplasm, regeneration and growth of blood vessels occurs not only in the bone undergoing intervention, but also in the surrounding tissues. The essence of the operation is the longitudinal osteotomy of the tibia, followed by the dosed traction of the formed bone "flakes" in the transverse direction. The efficiency of Ilizarov’s operation was 76%, it was proposed to combine the operation with sympathectomy and arterial reconstruction. However, the danger of fracture of the tibia during this intervention, the high probability of infection, the duration of treatment, determined the complexity of the use of this method [Alekseytsev V. Differentiated assessment of the results of revascularizing osteotrepanation in the treatment of patients with chronic obliterating diseases of the lower limb arteries. Ph.D. Novosibirsk - 2004].

Known methods for surgical treatment of patients with obliterating diseases of the vessels of the lower extremities with ischemia of the lower extremities: USSR N 1680092, class A61B 17/00, Zusmanovich V.I. and RF patent N 2093085, A61B 17/00, 17/56, A method for stimulating blood circulation in obliterating diseases of limb arteries, proposed by V. Shatohin. and Maryev A.Yu. The principle of treatment is to stimulate blood circulation by trepanation of the cortical plate before opening the bone marrow canal without causing injury to the bone marrow. In the second patent, a conductor is inserted into the distal trepanation opening, to the end of which a special device is attached for causing a dosed mechanical injury to the bone marrow (Babcock probe). The conductor along with the device is conducted along the medullary canal, which causes a dosed injury to the bone marrow.

The disadvantages of these surgical interventions are the short duration and uncontrollability of the stimulating effect on blood circulation and microcirculation. Trepanation holes in the bones caused by a thin drill do not provide complete bone marrow decompression, therefore, the period of blood circulation stimulation is limited.

A known method of revascularizing osteomyoplasty (Sukovatykh B.S. Experimental and clinical justification of revascularizing osteomyoplasty for the treatment of critical lower limb ischemia / B.S. Sukovatykh, L.N. Belikov, K.S. Magomedalieva // Bulletin of Surgery named after II Grekov , 2006. - No. 6. - S. 21-24). The method is as follows. A corticoectomy of the proximal part of the tibial diaphysis is performed on a 10 × 2 cm site. One of the muscles of the posterior tibia group (gastrocnemius, soleus) is mobilized by dissecting its fascial membrane, the fascia is separated from the muscle tissue while maintaining central circulation. Muscle tissue is placed in the formed bone cavity. The method provides good results, but it is quite traumatic, complex, requires the use of microsurgical techniques.

One of the last and most promising directions in the treatment of critical ischemia is the implementation of therapeutic angiogenesis - stimulation of the growth of blood vessels and collaterals in ischemic tissues [Bokeria L.A., Demidova O.A., Eremeeva M.V., Arakelyan B.C. The use of angiogenesis stimulants in the treatment of chronic lower limb ischemia. XIII All-Russian Congress of Cardiac Surgeons. Bulletin NTSSSH them. A.N. Bakuleva RAMS "Cardiovascular disease." 2007; 6: 296 .; Talitsky K.A., Bulkina O.S., Arefieva T.I. et al. The effectiveness of therapeutic angiogenesis in patients with chronic lower limb ischemia // Cellular transplantology and tissue engineering. - 2011 .-- T. VI. - Number 3. - S. 89-98; Shigematsu N., Yasuda K., Sasajima T. et al. Transfection of human HGF plasmid DNA improves limb salvage in Buergerʹs disease patients with critical limb ischemia. Int Angiol. 2011; 30 (2): 140-9.]. At the same time, synthesis of angiogenic growth factors (AFR) is activated in the ischemic focus, and endothelial progenitor cells mobilize from the bone marrow and migrate to the foci of neovascularization. Therapeutic angiogenesis is based on the introduction of ischemia (intramuscular, intravenous and intra-arterial administration):

- angiogenic factors (VEGF, FGF, transforming growth factor - TGF b, GM-CSF, etc.) (RF patent No. 2547692, RU No. 2426174) [11];

- genetic constructs that ensure the synthesis of angiogenic factors in ischemic limb tissue (RF patent No. 244979, RU No. 20081225416, RU No. 2008125409);

- implantation of stem (progenitor) cells (SC) that secrete various growth cells, including angiogenic factors.

However, the effectiveness of known methods of therapeutic angiogenesis was not too high [Yla-Herttuala S., Rissanen TT, Vajanto I. Vascular endothelial growth factors: biology and current status of clinical application in cardiovascular medicine. JMCC 2007. V. 49. P. 1015-26; Rissanen T.T., Yla-Herttuala S. Current status of cardiovascular gene therapy.

Mol. Ther. 2007. V. 15. P. 1233-47]. The main reason for the failure of monotherapy with angiogenic factors in their rapid destruction in the body, and their repeated administration causes a number of side effects, for example, severe vasodilation with the development of systemic hypotension and the occurrence of vascular neoplasms - hemangiomas [Makinen K., Manninen N., Hedman M., Matsi P., Mussalo N., Alhava E., Yla-Herttuala S. Increased vascularity detected by digital subtraction angiography after VEGF gene transfer to human lower limb artery: a randomized, placebo-controlled, double-blinded phase II study. Mol. Ther. 2002; 6: 127-133].

The use of angiogenic genetic constructs in CINC has a number of significant drawbacks. These include the rapid degradation of plasmids by blood and tissue nucleases, the extremely low transfection efficiency (the number of plasmids included in the recipient cells), the lack of ways to stop the excessive synthesis of angiogenic factor by transfected recipient cells, and the high risk of tumor formation due to uncontrolled entry of angiogenic factors into the systemic circulation [ Leppanen P., Kholova I. Short and long-term effects of hVEGF-A (165) in Creactivated transgenetic mice. Plos one. 2006; 1: 13.14], and simple mechanical mixing of the genes of various ADFs does not allow achieving reliable results [Cao R., Brakenhielm E., Pawliuk R. et al. Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF. Nat. Med. 2003. V. 9. P.604-13]. An immune response of the body to a protein synthesized in the body using a plasmid is also possible [Tang, D.C., DeVit, M., Johnston S.A. Genetic immunization is a simple method for eliciting an immune response. Nature. 1992; 356: 152-154.15].

The next direction in the implementation of the ideas of therapeutic angiogenesis in limb ischemia is the use of stem and other progenitor cell (SC) preparations [Bosiers M., Schneider P.A. Critical limb ischemia. N.-Y .: Informa Healthcare USA. 2009. 352 p., Armstrong L., Lako M., Buckley N., Lappin T.R., Murphy M.J., Nolta J.A., Pittenger M., Stojkovic M. Our top 10 developments in stem cell biology over the last 30 years. Stem Cells. 2012; 30 (1): 2-9]. Clinical trials of cell preparations have shown their safety. However, the effectiveness of such therapy was not so noticeable.

The fate and therapeutic effectiveness of SC implanted in the body is directly related to the method of their introduction.

After intra-arterial or intravenous administration, most SCs are retained in the vasculature at the precapillary level (92% for mesenchymal SCs) [Tota S., Wagner WR, Bowry S., Schwartz A., Villanueva F. Fate of cultured-expanded mesenchymal stem cells in the micro-vasculature: in vivo observations of cell kinetics. Circ. Res. 2009; 104 (3): 398,402]. This can lead to a significant blockade of blood flow (its decrease to 60%) [YoshidaM., Horimoto N., Mieno S. Intra-arterial bone marrow cell transplantation induces angiogenesis in rat hindlimb ischemia. Eur. Surg. Res. 2003; 35: 86-91.30]. In skeletal muscle, implanted cells last much longer. According to M.V. Kalashnikova and A.V. Belyavsky (2009), the safety of mesenchymal stem cells (MSCs) obtained from adipose tissue after their introduction into the calf muscles of mice and rats was 50-70% after 1 day and 5-10% after 1 week. No significant differences in the safety of implanted cells in normal and ischemic muscles were found, which is an argument in favor of the use in clinical practice of the technology of introducing SC directly into the muscles of the affected lower extremities.

The closest of the proposed methods for the technical essence and mechanisms for improving blood circulation in the ischemic limb are methods of treating chronic limb ischemia - a method of revascularizing osteotrepanation, involving multiple through and / or non-through osteotrepanation over the bones of the affected lower limb, starting with a fully supplied blood to its site, the introduction of medicinal drugs and the subsequent external physiotherapeutic effect (see book. F.N. Zusmanovich. "Revask laryngeal osteotrepanation in the treatment of patients with obliterating diseases of limbs. Kurgan. Publishing house of the Kurgan State Pedagogical Institute, 1996, pp. 23-26., copyright certificate SU No. 1680092, MKI-5: A61B 17/00, published on 09.30.1991. ), and a method for cell therapy of critical ischemia of the lower extremities using autogenous platelet-rich plasma (Dragunov A.G. Aleksandrov Yu.V. Khripunov S.A. Application of intratissue injection of autoplasma enriched with platelets (AOT) in the treatment of lower limb ischemia // Angiology Vascular Surgery, 2008. - V. 14. - №4. - S. 17-19).

According to the first method selected as the closest analogue, osteotrepanation is performed in the projection of biologically active points. Medicines are prescribed to the patient in the postoperative period. An external physiotherapeutic effect is prescribed from the first day after the operation. As a physiotherapeutic effect, UHF, EHF, UHF, magnet are prescribed.

However, this method is still not effective enough, since only the limbs applied on a limited segment, starting from the fully supplied area, using this technique, trepanation holes cannot provide sufficiently active stimulation of blood flow and do not take into account the progressive course of the obliterating process.

In addition, it is complicated by the fact that it requires additional knowledge, certain skills to identify projections of biologically active points. And the location in their projection of important anatomical formations (vessels and nerves), with the existing high probability of damage, represent this method and not safe enough.

It is believed that the application of trepanation holes stimulates neoangiogenesis in the ischemic limb due to the formation of a capillary network in the area of damage to the periosteum. However, the use of revascularizing osteotrepanation remains ineffective in 32-40% of patients, due to insufficient disclosure of collateral vascular networks (paraossal, muscle, intermuscular, paraarticular, skin) in response to the application of perforations in the tibia.

The essence of the second method consists in injecting autologous blood into the soft tissues of the lower extremities twice with an interval of 10-14 days in the amount of 60-80 ml in the foot and 150-180 ml in the lower leg. However, this method of treatment requires a long stay in the hospital, designed for 30 days, quite traumatic, due to the fact that this painful procedure is carried out 4 times in accordance with the description of the known method: on the 1st day and on the 14th day, the lower legs are treated, The 7th and 21st day are treated with feet. In addition, the method does not sufficiently improve collateral circulation and the adequate development of revascularization in the tissues of the lower extremities, which leads to various complications and insufficiently expected treatment results. For example, an increase in the distance without painful walking does not occur significantly.

The basis of the invention is the task of improving the results of limb preservation in patients with critical lower limb ischemia in the absence of direct revascularization conditions through a new combined surgical treatment aimed at escalating neoangiogenesis processes along the entire length of the affected limb.

The solution to this problem is provided by the fact that in the method of combined surgical stimulation of neoangiogenesis in chronic lower limb ischemia, including trepanation holes, through osteoperforative holes are performed throughout the limb, using a mosquito clip and bluntly passing through all layers of tissue to the bone, while a guide protective tube is inserted into the formed holes, into which a drill is installed; on the thigh, through 10 separate punctures of the skin and wide fascia of the thigh up to 1.0 cm long, on the outer surface, accesses to the outer surface of the femur are performed, while in the projection of the proximal epiphysis of the femur, from a level 5 cm below the greater trochanter, every 4- 5 cm in the distal direction on the outer surface exactly in the middle of the bone through the protective guide tube inserted to the bone with a drill with a diameter of 4.5 mm in the transverse direction in the center, there are three through perforated holes passing both cortical layers before admission of the drill guide content cancellous dyed a scarlet red; in the projection of the diaphysis in the transverse direction in the center of the outer surface at a distance of 4-5 cm from one another, 4 injuries are performed by drilling in the outer layer of the periosteum without failure in the medullary canal; 3 perforated holes of the distal metaepiphysis are performed at a distance of 4-5 cm from each other in the proximal direction, projecting the first bone drilling from the level of the upper edge of the patella; on the lower leg, through perforations of the proximal and distal metaepiphyses of the tibia, 3 on each, are performed in the same way as on the femur, but the direction of drilling is made from the inner surface of the lower leg; damage by drilling in the outer layer of the periosteum, without failure in the medullary canal, in the diaphyseal part on the medial surface of the tibia, also perform 4 damage by drilling at a distance of 4-5 cm from each other, through the muscle mass of the anterior region of the leg; on the foot from one injection, on the inner surface of the heel, with a 1.5 mm Kirschner needle, the calcaneus is perforated “fan-like”, through, without removing the needle from the injection three times in different directions, but from the side of the metatarsal bone, up to 3 cm between the injections transverse through tunneling of the I-II-III-IV metatarsal bones twice; through the produced holes with a 20.0 ml syringe, an autoconcentrate of stem cells from peripheral blood is injected, we offend a volume of 100 ml into the soft tissues and to the zones of osteoperforations on the thigh, on the lower leg and in addition to the muscle mass of the anterior, external and posterior bone-fibrous vaginas, on the foot in I-II-III-IV intertarsal intervals.

To obtain the maximum positive result of the operation, it is carried out on the thigh, lower leg and foot, i.e. on the whole limb.

To perform the operation, in addition to general surgical instruments, it is necessary to have a drill with an adjustable shaft speed from 50 to 1600 rpm, a drill 160 mm long and a diameter of 4.5 mm with a sharpening angle of 120 °, and a Kirschner needle (1.5 mm), and for the collection of autologous stem cell concentrate from peripheral blood, a kit (column) for producing peripheral stem cells and a blood cell separator.

Special preoperative preparation of the patient is not required. The duration of stem cell sampling by a blood cell separator is 50-60 minutes, performed immediately before surgery. The duration of the operation with the introduction of stem cells is about 40-60 minutes. The operation is performed under general anesthesia.

Patients are allowed to get up and maximize walking from the first day. Sutures are removed after 7-8 days.

The method is as follows: The position of the patient lying on his back. After processing the surgical field with iodonate. Alternately at the previously designated projection points for drilling, dissect the skin, subcutaneous tissue, fascia. A mosquito clamp is inserted into the wound and bluntly passes through all layers of tissue to the bone. In this case, as a rule, it is possible to avoid damage to the neurovascular formations. A guide protective tube is inserted into the formed channel, into which the drill is installed, strictly perpendicular to the bone,

drill at low speeds, then increasing them. After the sensation of the failure of the drill into the medullary canal, the drill is carried out to the contralateral edge of the bone and drilling creates a through hole. If the outer layer of the periosteum of the epiphyseal part of the tubular bones is damaged by drilling, it is necessary to give the axial load with extreme caution and dosage, since the resistance of the spongy bone is quite low.

On the thigh: through separate punctures-incisions (10) of the skin and the wide fascia of the thigh up to 1.0 cm long on the outer surface, a mosquito clip bluntly passes through all layers of tissues and accesses the outer surface of the femur. In the projection of the proximal epiphysis of the femur, from a level 5 cm below the greater trochanter, every 4-5 cm in the distal direction, along the outer surface exactly in the middle of the bone, through the protective guide tube inserted to the bone with a drill with a diameter of 4.5 mm in the transverse direction three through perforated holes are made in the center, passing both cortical layers. The reference point in the epiphyseal part of the bone is the entry from the guide drill, the contents of the spongy substance, painted in scarlet color (red bone marrow).

In the projection of the diaphysis, in the transverse direction, in the center of the outer surface, at a distance of 4-5 cm from one another, drilling-damage to the outer layer of the periosteum (4) is performed without failure in the medullary canal.

Perforated holes of the distal metaepiphysis (3) are performed at a distance of 4-5 cm from each other, in the proximal direction, projecting the first bone drilling from the level of the upper edge of the patella.

On the shin: Through perforations of the proximal and distal metaepiphyses of the tibia, 3 on each, are performed in the same way as on the femur, but the direction of drilling is made from the inner surface of the shin.

Damage by drilling the outer layer of the periosteum (4), without failure in the medullary canal, in the diaphyseal part on the medial surface of the tibia, is also produced at a distance of 4-5 cm from one another, through the muscle mass of the anterior region of the leg.

On the foot: From one injection, on the inner surface of the heel, with a Kirschner needle (1.5 mm), the calcaneus is perforated “fan-like”, through without removing the needle from the injection three times in three directions in three directions in different directions. From the side of the I metatarsal bone, at a distance of up to 3 cm between the injections, transverse through tunneling of the I-II-III-IV metatarsal bones is performed twice.

Through the injections made with a 20.0 ml syringe, an autoconcentrate of stem cells from peripheral blood (total volume of 100 ml) is injected into the soft tissues (intramuscularly) and to the zones of osteoperforations on the thigh, on the lower leg, and additionally into the muscle mass of the anterior, external and posterior bone-fibrous vaginas, on the foot in I-II-III-IV intertarsal spaces. Sutured skin wounds. The surgical field is treated with alcohol with iodine. Wrap a limb with an alcohol towel. Impose aseptic dressing.

Technical result: Mechanical creation of perforations, bone trauma, is characterized by the formation of reflex arterial hyperemia in the injury zone with the opening of the so-called reserve vessels, the expansion of the lumen of the preserved major vessels and precapillaries. Perforations in the metaepiphyseal part of the tubular bones facilitate the migration of mobilized endothelial progenitor cells from the red bone marrow to the ischemia site, where, under the influence of activated ischemia synthesis of angiogenic growth factors (AFR), differentiable SCs contribute to the development of neovascularization in the immediate vicinity of the main-nodal areas of division of the main arteries which creates the prerequisites for the development of a new microvasculature - neoangiogenesis. In the process of osteogenesis of injured areas in the bone,

Against the background of the formation of the smallest vessels that do not have a characteristic identification, it seems that vasculogenesis is stimulated with the participation of a specific CD 34 subgroup in an autologous stem cell concentrate.

By increasing the density and total area of the capillary network, the state of microcirculation improves, creating compensatory opportunities for collateral microcirculatory blood flow throughout the ischemic limb.

This combined method, expanding the reserve vessels, precapillaries and lumen of the preserved vessels, in combination with the stimulation of local neoangiogenesis processes, significantly increases the capacity of the peripheral vascular bed and perfusion of the entire limb segment.

Thus, the proposed high-tech treatment method can be effectively used to treat chronic lower limb ischemia caused by damage to the distal vascular bed, when the use of direct reconstructive operations on the vessels is impossible, and pharmacological, physical and biological methods of stimulating collateral circulation remain ineffective, as an alternative to amputation limbs.

Example 1

Observation 1. B. K., 56 years old, was admitted to the department of vascular surgery with a diagnosis of Generalized atherosclerosis. Obliterating atherosclerosis of the arteries of the lower extremities. Lerish's syndrome. Aorto-femoral bifurcation bypass, left-side lumbar sympathectomy from 2002. Thrombosis of the left jaw shunt. Thrombectomy from the left junction of the shunt, relaparotomy, transprotic thrombectomy from the central anastomosis, femoral-popliteal left-side autogenous bypass surgery from 2004. Acute thrombosis of the right jaw of the bifurcation shunt from 12/29/2012, Right-sided lumbar sympatectomy boresection -femoral right prosthesis with anastomosis to the left jaw. Femoral-popliteal right-sided bypass graft reversed from 01.2012. Occlusion of the right superficial femoral artery. Acute thrombosis of the right jaw of the prosthesis (from 03.15.2014). Thrombintimectomy from the right jaw of the aorto-femoral bifurcation shunt. Femoral-popliteal right-sided resection of PTFE with a 6 mm prosthesis dated 03/21/2014. Revised distal anastomosis of the femoral-popliteal shunt on the right. Thrombectomy. Prosthetics of the distal part of the shunt with reanastomosis to the popliteal artery. Fasciotomy of the right lower leg of March 21, 2014. Thrombectomy of the right popliteal artery, arteries of the right lower leg, right femoral-popliteal resuscitation with an artificial explant 8 mm (B Braun) above the gap of the knee joint, removal of the thrombosed shunt from 11/18/2014 Recanalization, balloon angioplasty and stenting of the arteries of the right lower limb from 11/22/2014

Complication of the underlying disease: Thrombosis of the femoral-popliteal shunt to the right of 06/01/2016. Critical ischemia of the right lower limb, grade III.

Concomitant diseases: Coronary heart disease. Hypertension of the II stage, arterial normotension, an additional risk of cardiovascular complications is high. Obesity of 1 degree, android form, stable stage.

Sick for 15 years, was admitted with complaints of pain in the calf muscle in the right lower limb (distance without pain walking 50 m); moderate pallor of the right foot, its cooling. From the anamnesis: in 2002, for Lerish’s syndrome, ABBS was performed, left-sided PSE. In 2004, thrombectomy from the left branch of the prosthesis, thrombectomy from the central anastomosis, autologous BPS from the left. In 2012, a resection of the central jaw ABBS, prosthetic-femoral on the right with the application of an anastomosis to the left jaw prosthetics; BPSh on the right autogenous. 03/15/14, - BPSh thrombosis on the right, 03/21/14, - revision of the distal BPSh anastomosis on the right, reconstruction of the distal anastomosis. In July and September 2014, he was hospitalized at the clinic for inflammatory infiltrate of the upper third of the right thigh. On October 23, 2014, he again noted the appearance of a painful formation in / 3 of the right thigh. 11/18/2014 thrombosis of BP shunt of the right lower limb, thrombectomy from the right popliteal artery, arteries of the right lower leg, right-sided femoral-popliteal resuscitation with an artificial explant above the gap of the knee joint was performed. Removal of a thrombosed shunt. Postoperative wounds healed by first intention. However, according to CT angiography, the patient has hemodynamically significant stenosis below the distal anastomosis. 12/22/14, the operation was performed balloon angioplasty and stenting of the arteries of the right lower limb (femoral-popliteal shunt). In January-February 2015, neovasculogen was introduced into the muscle mass of the right lower leg.

06/01/2016, after a prolonged stay in a bent position on the knees, a pain suddenly appeared in the right lower limb. The patient noted a cooling of the right foot, a cyanotic shade of the I-III fingers, hyperemia of the foot and lower third of the leg.

With an external examination of trophic ulcers on the right lower limb, palpation of the muscles of the legs is painless. There was a lack of hair on both feet and on the right lower leg. The right foot is cooler to the touch than the left. With thermography, the temperature on the right foot is less than 4 ° C compared with the left. Movement in the joints in full, the left ankle joint is limited, painful. Pulsation of arteries on the left lower limb is determined in the projection of the femoral, popliteal (weakened) and anterior tibial arteries; on the right lower limb - is determined only in the projection of the femoral artery (weakened). The pulsation of the main arteries of the upper extremities is distinct at all levels.

When rheovasography revealed a sharp decrease in the rheographic index (RI). RI - 0.01. The sample with nitroglycerin did not lead to an increase in the rheographic index. According to veno-occlusion plethysmography, the volumetric blood flow on the left leg was 1.1 ml per min / 100 g. After a 3-minute ischemic test, there was no increase in blood flow.

According to UDG, Vmax + (m / s) over the posterior tibial artery was 0.14. Vmax- (m / s) - 0. The ripple index (IP) was 2.80. The ankle-brachial index (LGHI) was 0.21 on the left and more than 0.3 on the right. When performing laser Doppler ultrasound, the capillary blood flow index was 0.38 on the left and 0.68 on the right. Based on the results of duplex scanning, an extended occlusion of both lower leg arteries was established on the left and right. This patient had an isolated atherosclerotic lesion of the tibial arteries of both limbs with decompensation of impaired blood circulation in the left lower limb. Reconstructive surgery was not feasible.

06.06. Thigh-popliteal shunt thrombectomy on the right. Unsatisfactory antegrade blood flow was obtained, retrograde blood flow was not obtained. An attempt was made to bougiege proximal and distal anastomoses, without effect. A decision was made to complete the operation.

10.06. Revision of the central anastomosis of the femoral-popliteal shunt on the right. Removing stents from the femoral-popliteal shunt and right jaw of the aorto-femoral bifurcation shunt. Femoral artery endarterectomy with profundoplasty artificial patch. As a result of surgical treatment, pulsation over the common femoral artery was restored. According to the result of intraoperative angiography, the absence of main blood flow according to PBA, PKA, PBA, ZBA, MBA, "depletion" of contrasting collateral blood flow.

Given the multi-storey form of lesions of the vascular bed of the right lower limb, repeated reconstructive surgical interventions on the arteries of the right lower limb, the progression of the underlying disease and the futility of further conservative therapy and surgical treatment methods to save the right lower limb 22.06. the patient underwent surgery - Surgical stimulation of neovasculogenesis of the right lower limb. The operation was performed according to the method described above. Perforation holes, drilling-damage to the outer layer of the periosteum were made at a distance of 4-5 cm. One from the other.

The activation of the patient began to be performed on the same day, the ward regimen. Went without crutches with the onset of the foot. The next day, activation was expanded. Pain at rest stopped immediately after surgery. The distance gradually increased from 50 m to 200 m upon discharge. The patient was discharged from the hospital on the 4th day after the last surgical treatment.

At discharge, the increase in RI on the foot and lower leg was negligible. LPI increased by 30%. The capillary blood flow index increased to 0.68.

After 3 months, the patient was hospitalized for examination and subsequent staged treatment. On radiographs of bones and CT bones of the right lower limb, the preservation of perforation channels in the epiphyseal sections of the bones and the damaged supraorbital in the diaphyseal sections is noted. Blood circulation in the right lower limb is subcompensated. Without painful distance traveled up to 500 m.

Control angiography of the lower extremities: Right lower limb - BOTH and GBA contrasts satisfactorily, without defects. Active filling of the BOTH branches is visualized. Occlusion of PBA from the mouth. PCA, the tibioperoneal trunk, ZBBA, PBA are filled fragmentarily from the appearing, pronounced collateral vessels on the thigh and lower leg. The contrasting of the plantar arch was revealed. Left lower limb - BOTH contrasts distinctly. GBA occlusion. Functioning femoral-popliteal shunt. PCA is contrasted with significant defects (atherosclerotically altered). The lower leg arteries are represented by an atherosclerotically altered ZBA to the lower third of the lower leg.

A high-frequency Doppler study in comparison with the initial data at discharge is a transient decrease in systolic velocity (cm / s) with its subsequent increase, which indicates the initial progression of stenosis of the arteries of the right lower limb, followed by its slow recovery. The average speed (cm / s) and diastolic speed (cm / s) are characterized by a progressive decrease, which is associated with the slow development of collateral blood flow. Gosling and Purselo indices showed steady growth against the background of the treatment.

Laser Doppler flowmetry. Three months after the study, its value began to increase, which indicates the development of collaterals.

Volumetric sphygmography. Initially, R-CAVI was 8.8; a week after the study, it decreased to 3.7. When conducting the study after three months, it further decreased to 2.8. However, given the pronounced atherosclerotic lesion of the arteries of the right lower limb, there is a measurement error. The results indicate a decrease in vascular stiffness on the affected right lower limb.

The temperature of the right lower limb showed an increase in the foot to 8 ° C (from 26 ° C to 34 ° C), on the lower leg to 3 ° C (from 29 ° C to 32 ° C).

In order to increase the effect of the development of collateral blood flow on the right lower limb, the second stage of the patient was repeated introduction of an autoconcentrate of stem cells from peripheral blood into the tissue array. Given the multi-storey form of lesions of the vascular bed and the left lower limb, repeated reconstructive surgical interventions against the background of the progression of the underlying disease, the futility of further conservative therapy and surgical treatment methods, surgical combined stimulation of neovasculogenesis on the left lower limb was simultaneously performed to save the left lower limb according to the described method.

The patient was examined 2 years after surgery. Blood circulation in both lower extremities is compensated. There is stage I circulatory disorders. Passable pain-free distance is more than 500 m.

Example 2

Observation 2. B. S., 64 years old, was admitted to the department of vascular surgery with a diagnosis of Obliterating atherosclerosis of the arteries of the lower extremities. Occlusion of the right superficial femoral artery in the lower third of the thigh, popliteal artery, lower leg arteries.

Complication of the underlying disease: Critical ischemia of the right lower limb, IV degree.

Concomitant diseases: Stage II hypertension, arterial normotension. Type 2 diabetes mellitus, mild, compensated.

Sick for 1.5 years, was admitted with complaints of pain in the calf muscles in the right lower limb at rest, night pain, forcing to sleep with a lowered limb (distance without pain walking up to 200 m.); pallor of the right foot, its cooling, wet trophic ulcer of the second toe of the right foot. From the anamnesis: was treated on an outpatient basis under the supervision of a polyclinic doctor. Deterioration arose suddenly a month ago, was treated independently. In connection with the increase in pain, he turned to a vascular surgeon.

On external examination: a trophic wet ulcer on the inner surface of the main phalanx of the second toe of the right foot, palpation of the muscles of the right lower leg is moderately painful. The right foot is cooler to the touch than the left. With thermography, the temperature on the right foot is 5 ° C lower than the left (t = 29 ° C). Joint movements in full. Pulsation of arteries on the left lower limb is determined at all typical points, throughout; on the right lower limb is determined only in the projection of the femoral artery. The pulsation of the main arteries of the upper extremities is distinct at all levels. Conclusion of computer angiography of the lower extremities: occlusion of the arteries of the right lower limb. Occlusion of the superficial femoral artery in the lower third of the thigh, popliteal artery, lower leg arteries. Given the distal form of damage to the vascular bed of the right lower limb, the progression of the underlying disease and the futility of further conservative therapy and methods of direct reconstructive surgical treatment, the patient underwent surgery - Surgical stimulation of neovasculogenesis of the right lower limb - to save the right lower limb. The operation was performed according to the method described above. Perforation holes, drilling-damage to the outer layer of the periosteum were made at a distance of 2-3 cm from one another.

Activation of the patient began to perform in the early postoperative period, ward mode. Went without crutches with the onset of the foot. From the first day, activation was expanded. Pain at rest stopped immediately after surgery. The distance gradually increased from 200 m to 400 m upon discharge. The patient was discharged from the hospital on the 7th day after removal of skin sutures.

In order to increase the effect of the development of collateral blood flow on the right lower limb, the second stage of the patient was repeated introduction of an autoconcentrate of stem cells from peripheral blood into the tissue array (therapeutic neovasculogenesis).

On examination, the patient noted a positive trend from the treatment expressed in the absence of pain in the right lower limb at night and at rest, an increase in the intensity of painless walking to 700 m, a decrease in the duration of necessary rest when walking to 2-3 minutes from the previous 15-20 before surgery, epithelization ulcers of the second toe of the right foot. The temperature of the right lower limb showed an increase in the foot to 3 ° C (from 29 ° C to 32 ° C).

During the control computer-topographic perfusion of the middle third of the legs (before the operation, after 1 and 3 months), an increase in the volumetric blood flow of both limbs, a decrease in the permeability time were revealed, the changes were most pronounced in the inner muscle group of the right leg, the time of appearance of blood in the bill increased the time to reach the peak of the contrast medium.

The obtained data of rheovasography of the right lower limb (lower leg / foot) after 3 months indicate an increase in vascular tone of blood vessels (PST (%) from 32.07 / 35.62 to 37.55 / 42.22), an increase in the amount of blood delivered per 100 cm3 min (Vq100 (ml / min) from 2.72 / 1.72 to 3.74 / 3.26), acceleration of the fast filling period (FSP (%) from 5.10 / 5.82 to 7.96 / 7, 84), increasing the peripheral resistance index (IPS (%) from 74.87 / 28.84 to 138.67 / 110.16).

According to this method of treatment, assistance was provided to 7 patients in 1 clinic of surgery (improvement of doctors) of VMedA them. CM. Kirov In 6 patients, the cause of the disease was atherosclerosis obliterans, 1 patient with obliterating endarteritis, complicated by the development of critical lower limb ischemia. Of 6 patients with IV tbsp. limon ischemia according to Fontaine, after treatment with the proposed method, a positive result for the first 6 months was observed in 5 patients. Long-term results (1-2 years after treatment) were monitored in 5 patients. In one patient, operated prophylactically on the contralateral limb, after 2 years, due to the progression of the underlying disease (occlusion of one of the ABBS branches with lack of blood flow in all femoral vessels and lower leg vessels), surgical treatment according to the above procedure was repeated. All 6 patients with IV tbsp. limb ischemia succeeded in avoiding high limb amputation.

Example 3

Observation 3. B. B. 67 years old was admitted to the Department of Vascular Surgery with a diagnosis of Generalized atherosclerosis of the aorta, coronary arteries and lower limb arteries. Obliterating atherosclerosis of the arteries of both lower extremities. Occlusion of the right internal iliac artery, right superficial femoral artery, subocclusion of the left superficial femoral artery, 65% stenosis of the right popliteal artery, 50% stenosis of the left popliteal artery, multilevel stenosis (before occlusion) of the arteries of both lower legs.

Complication of the underlying disease: Chronic arterial ischemia of the left lower limb, grade 2B.

Background disease: Type 2 diabetes mellitus, target HbAIc level of 7% Concomitant diseases: Coronary heart disease. Hypertension of the III stage, arterial hypertension of the I degree, additional risk of cardiovascular complications is high. Incidentaloma of both adrenal glands.

Sick for 3 years, was admitted with complaints of pain in the calf muscles of both lower extremities, more on the left (distance without painful walking up to 100 m.); cooling of the fingers and left foot, numbness of the thumb of the left foot. From the anamnesis: did not seek medical help. While being examined in a therapeutic hospital, he was first consulted by a vascular surgeon. On external examination: the color of the skin is normal, clean. Both lower limbs are warm to the touch, except for the fingers of the left foot - cool pale. Palpation of the leg muscles is painless. Joint movements in full. On both lower extremities, pulsation is determined only in the projection of the femoral arteries. With thermography, the temperature on the left foot is 5 ° C lower than that on the right (t = 29 ° C). The pulsation of the main arteries of the upper extremities is distinct at all levels.

Conclusion of computer angiography of the lower extremities: common atherosclerosis with occlusion of the right internal iliac artery, right superficial femoral artery; subocclusion of the left superficial femoral artery, occlusion of the anterior tibial artery on the left. Stenosis of the right popliteal artery 66%, left popliteal artery 50%. Multilevel stenosis of the anterior tibial artery on the right, single stenosis of both posterior tibial arteries.

Given the multilevel, distal form of the lesion of the vascular bed of the left lower limb, the progression of the underlying disease, the futility of further conservative therapy and methods of direct reconstructive surgical treatment, to save the left lower limb and to improve regional blood circulation in the left lower limb, the patient underwent surgery - Surgical stimulation of neovasculogenesis left lower limb. The operation was performed according to the method described above. Perforation holes, drilling-damage to the outer layer of the periosteum were made at a distance of 5-6 cm. One from the other.

Activation of the patient began to perform in the early postoperative period, ward mode. Went without crutches with the onset of the foot. From the first day, activation was expanded. Complaints of moderate pain in the left lower limb persisted. Sensitivity of the left toe appeared. The distance gradually increased from 100 m to 300 m upon discharge. The patient was discharged from the hospital on the 7th day after removal of skin sutures.

The temperature of the left lower limb showed an increase in the foot to 3 ° C (from 29 ° C to 32 ° C).

During follow-up examinations after 10 days 1 and 3 months, the patient did not increase the distance without pain walking, remaining within the distance of 300 m. The feeling of cooling left foot remained.

The obtained data of rheovasography of the lower leg of the lower extremity after 1 and 3 months indicate a slight increase in the vascular tone of the vessels on the lower leg (PST (%) from 37.94 to 39.77 (1 month), 39/24 (3 months)), the amount of blood flowing per 100 cm3 per min (Vq100 (ml / min) from 2.39 to 3.13 (1 month), 3.17 (3 months)), a slight acceleration of the fast filling period (PBN (%) from 5.79 to 6.40 (1 month), 6.75 (3 months)), a decrease in the peripheral resistance index (IPS (%) from 143.09 to 48.02 (1 month), 125.44 (3 months).

According to this method of treatment, assistance was provided to 7 patients in 1 clinic of surgery (improvement of doctors) of VMedA them. CM. Kirov In 6 patients, the cause of the disease was atherosclerosis obliterans, 1 patient with obliterating endarteritis, complicated by the development of critical lower limb ischemia. Of 6 patients with IV tbsp. limon ischemia according to Fontaine, after treatment with the proposed method, a positive result for the first 6 months was observed in 5 patients. Long-term results (1-2 years after treatment) were monitored in 5 patients. In one patient, operated prophylactically on the contralateral limb, after 2 years, due to the progression of the underlying disease (occlusion of one of the ABBS branches with lack of blood flow in all femoral vessels and lower leg vessels), surgical treatment according to the above procedure was repeated. All 6 patients with IV tbsp. limb ischemia succeeded in avoiding high limb amputation.

Claims (1)

A method of combined surgical stimulation of neoangiogenesis in chronic lower limb ischemia, including trepanation holes, characterized in that through osteoperforative holes are performed throughout the limb using a mosquito clip and bluntly passing through all layers of tissue to the bone, and inserted into the formed holes a guide protective tube into which the drill is mounted; on the thigh, through 10 separate punctures of the skin and wide fascia of the thigh up to 1.0 cm long, on the outer surface, accesses to the outer surface of the femur are performed, while in the projection of the proximal epiphysis of the femur, from a level 5 cm below the greater trochanter, every 4- 5 cm in the distal direction on the outer surface exactly in the middle of the bone through the protective guide tube inserted to the bone with a drill with a diameter of 4.5 mm in the transverse direction in the center, there are three through perforated holes passing both cortical layers before admission of the drill guide content cancellous dyed a scarlet red; in the projection of the diaphysis in the transverse direction in the center of the outer surface at a distance of 4-5 cm from one another, 4 injuries are performed by drilling in the outer layer of the periosteum without failure in the medullary canal; 3 perforated holes of the distal metaepiphysis are performed at a distance of 4-5 cm from each other in the proximal direction, projecting the first bone drilling from the level of the upper edge of the patella; on the lower leg, through perforations of the proximal and distal metaepiphyses of the tibia, 3 on each, are performed in the same way as on the femur, but the direction of drilling is made from the inner surface of the lower leg; 4 damage by drilling in the outer layer of the periosteum, without failure in the medullary canal, in the diaphyseal part on the medial surface of the tibia, is also performed at a distance of 4-5 cm from each other, through the muscle mass of the anterior region of the leg; on the foot from one injection, on the inner surface of the heel, with a 1.5 mm Kirschner needle, the calcaneus is perforated “fan-like”, through, without removing the needle from the injection three times in different directions, but from the side of the metatarsal bone, up to 3 cm between the injections transverse through tunneling of the I-II-III-IV metatarsal bones twice; through the produced holes with a 20.0 ml syringe, a 100 ml hardware autoconcentrate of stem cells is introduced into the soft tissues and to the zones of osteoperforations on the thigh, on the lower leg and in addition to the muscle mass of the anterior, external and posterior bone-fibrous vaginas, on the foot in I- II-III-IV intertarsal spaces.